Dunn and colleagues hypothesized that genetic variability in genes related to steatosis contribute to the heterogeneous clinical recovery of patients with HCV cirrhosis after DAA treatment.

"Our working hypothesis is that patients with a genetic disposition to NASH (non-alcoholic steatohepatitis)…continue to undergo steatohepatitis-like injury and therefore fail to recover," Dunn told MD Magazine®.

The investigators identified a study population of 56 HCV patients who had attained SVR with DAA treatment but remained with Child-Pugh-Turcott (CPT) class B or C cirrhosis. A cheek swab was collected from each to determine genotype, and 3 single nucleotide polymorphisms (SNP) linked to steatosis: rs738409 of the Palatin-Like Phospholipase Domain-Containing 3 (PNPLA3) gene; rs58542926 of Transmembrane-6-Superfamily-2 (TM6SF2); and rs641738 of Membrane-bound O-acyltransferase Domain-Containing 7 (MBOAT7).

Dunn and colleagues reported that the PNPLA3 genotype CC had more overall CPT improvement on average than either the CG or GG genotypes. PNPLA3 CG/GG were associated with slower biochemical recovery (with higher MELD scores) and slower clinical recovery (higher CPT scores). In addition, hepatic encephalopathy and elevated bilirubin were more prominent in patients with the PNPLA3 CG/GG compared with the PNPLA3 CC genotype. The rs738409 SNP of PNPLA3 was identified in a subgroup of patients with suboptimal clinical recovery, but the results with rs5854296 and rs641738 were not significant.

Although the study linked PNPLA3 CG/GG with a subgroup of patients with decompensated HCV cirrhosis having suboptimal clinical recovery despite SVR, Dunn indicated that clinical screening for these apparently unfavorable PNPLA3 genotypes, to help target liver transplantation candidates for example, is not yet warranted.

"The effect of PNPLA3 is relatively modest compared to the measurable degree of liver decompensation," Dunn explained. "Currently, patients with a MELD score of about 14 undergo a liver transplant evaluation. Having an unfavorable PNPLA3 genotype is roughly equivalent to having 2 points higher MELD score."

"This kind of study will be very useful clinically when we can put together a panel of genetic scores to predict survival collectively," Dunn said.